1. Field of the Invention
The present invention relates to a method for exhaled breath analysis in which a variety of components included in exhaled breath are concentrated by electrostatic atomization and analyzed.
2. Related Art
In exhaled breaths, water, nitrogen, oxygen and carbon dioxide, as well as metabolic components, and minor components such as volatile organic compounds and volatile sulfur compound are included. For example, alcohols, ketones, aldehydes, amines, aromatic hydrocarbons, fatty acids, isoprenes, mercaptans and the like, and derivatives thereof may be included.
Some correlations between a disease and the minor components included in the exhaled breath have been perceived. Research achievements suggesting the correlation between a disease and components in the exhaled breath have also been reported (Nonpatent Document 1, Nonpatent Document 2, Nonpatent Document 3, and Nonpatent Document 4). Unlike blood testing, the exhaled breath analysis enables examination without leading any physical and/or mental pain to the subjects, therefore, applications in the medical field such as diagnoses, follow up of postoperative course, decision of therapeutic strategies and the like are expected.
However, the concentration of the exhaled breath components suggested to correlate with a disease is extremely trace, which is generally at a level of from ppm to ppt (Nonpatent Document 4).
Thus, according to conventional breath analysis apparatuses, procedures in which the analysis efficiently performed by any of known techniques such as a method of cold condensation of exhaled breath, a method of capturing/concentrating the exhaled breath components to a trapping agent, or the like have been adopted.
For example, in a well-known method of cold condensation of the exhaled breath, a thermoelectric element is used (Patent Document 1). FIG. 11 shows an apparatus for cold condensation of exhaled breath disclosed in Patent Document 1.
In the apparatus for cold condensation of exhaled breath, the exhaled breath blown therein by a subject is cooled, and the condensate thereof is collected. The apparatus for cold condensation of exhaled breath includes breath passage tube 911, condensate collecting vessel 904, and thermoelectric element 903. The thermoelectric element 903 is connected to the condensate collecting vessel 904 via thermal conductor 902. The breath passage tube 911 and the condensate collecting vessel 904 are provided in an attachable/detachable manner. The breath passage tube 911 is provided with backflow prevention device 908 having two unidirectional valves, and is provided with flow meter 916 for measuring the volume of the exhaled breath blown into the apparatus.
The apparatus for cold condensation of exhaled breath shown in FIG. 11 is one of generally employed apparatuses since it can be handled comparably simply, although a long time period for obtaining the condensate in an amount needed for the analysis may be required.
As an alternative method, Patent Document 2 discloses an example of a concentration technique using electrospraying. This method executes concentration by electrospraying of a nonvolatile dilute biomolecule solution to volatilize the solvent in the mist, and thus can be used also in concentration of nonvolatile components included in the exhaled breath. Exemplary means for concentrating biological molecule solutions disclosed in Patent Document 2 is shown in FIG. 12.
By the electrospraying apparatus shown in FIG. 12, deposit of the nonvolatile substance including biomacromolecules is obtained. This deposit may be used for determining the interaction of the deposit of the nonvolatile substance with other substance. Further, Patent Document 2 discloses that the deposition of biological molecules by the electrospraying can be also utilized as means for microconcentration of dilute biomolecule solutions.    Nonpatent Document 1: THE LANCET Vol. 353, pp. 1930-1933 (1999)    Nonpatent Document 2: ANALYTICAL BIOCHEMISTRY Vol. 247, pp. 272-278 (1997)    Nonpatent Document 3: The American Journal of Cardiology pp. 1593-1594 (2004)    Nonpatent Document 4: Respiratory Physiology & Neurobiology Vol. 145, pp. 295-300 (2005)    Patent Document 1: Japanese Unexamined Patent Application, First Publication No. 2004-361160 (p. 6, FIG. 1)    Patent Document 2: Japanese Unexamined Patent Application, First Publication (translation of PCT Application) No. 2002-511792 (pp. 31, lines 12 to 13, p. 78, FIG. 9)    Patent Document 3: United States Patent Application, Publication No. 2004/0210154 (particularly, paragraph No. 0054)    Patent Document 4: Japanese Unexamined Patent Application, First Publication No. 2007-033388 (particularly, paragraph Nos. 0002 to 0005)    Patent Document 5: Japanese Patent No. 3952052